In humans and animals even brief exposure to an odor produces long-lasting memories. In rodents, odor memories are acquired with one-trial learning and last for weeks. Although odor memories are thought to be primarily formed and/or stored in piriform cortex, data from rats suggest that certain aspects of olfactory learning and memory take place in the main olfactory bulb (MOB). Despite behavioral studies, there is virtually no information about the ability of olfactory input to modify the strength of sensory synapses in MOB. Similarly, there is scant evidence for neural substrates of learning and memory, such as long-term potentiation (LTP), in MOB. My new preliminary data demonstrate that brief, high frequency bursts (theta-burst stimulation, TBS) of olfactory nerve (ON) stimulation produce robust, long-term changes in the strength of neurotransmission at ON synapses in the glomeruli, the first site of synaptic processing in the olfactory system. This plasticity is differentially expressed by distinct MOB neuronal subtypes: (1) ON synapses with external tufted cells (ETCs) and mitral cells (MCs) exhibit LTP, and (2) ON synapses with inhibitory periglomerular cells (PGCs) exhibit long-term depression (LTD). Based on these and other new findings, I hypothesize that brief bursts of ON activity produce LTP at synapses with excitatory MOB neurons. I hypothesize that this will amplify glomerular output, via MCs, to higher order olfactory cortical structures. The LTP may involve, or be mediated by, a parallel decrease (i.e., LTD) in the excitability of local glomerular inhibitory interneurons. These hypotheses will be tested at the cellular and circuit level using patch clamp electrophysiology in rodent MOB slices. The overarching goal of this proposal is to elucidate the activity-dependant plasticity of sensory synapses in the olfactory bulb. Olfactory deficits occur with aging and several neurological disorders. The proposed research will lead to a better understanding of olfactory processing that may facilitate treatment of olfactory deficits. The overarching goal of this proposal is to elucidate activity-dependant plasticity of sensory synapses in the olfactory bulb. Activity-dependent regulation, including long-term potentiation, of sensory input to the bulb is likely to play important roles in olfactory learning and formation of odor memories. Olfactory deficits occur with aging and several neurological disorders. The proposed research will lead to a better understanding of olfactory processing that may facilitate treatment of olfactory deficits. [unreadable] [unreadable] [unreadable]